Anti-Inflammatory and Tau Phosphorylation-Inhibitory Effects of Eupatin

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 23; p. 5652
• Main Authors: Chou, Ching-Hsuan, Hsu, Kai-Cheng, Lin, Tony Eight, Yang, Chia-Ron
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30-11-2020; MDPI
• Subjects: Alzheimer's disease; Animals; Anti-Inflammatory Agents - pharmacology; Apoptosis; Cognitive ability; Cyclin-dependent kinases; Cytotoxicity; Disease; Drugs; eupatin; Flavonoids; Flavonoids - pharmacology; Glycogen; Glycogen synthase kinase 3; glycogen synthase kinase 3β; Glycogens; Health services; Hydrocarbons; Hydrogen bonds; Inflammation; Interleukin 6; Kinases; Lipopolysaccharides; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Macrophages - pathology; Mice; Microglia; Microglia - drug effects; Microglia - metabolism; Microglia - pathology; Molecular docking; Molecular Docking Simulation; Natural products; Neurodegeneration; neuroinflammation; Neuroprotection; Neuroprotective Agents - pharmacology; Neurotoxicity; Nitric oxide; Nitric-oxide synthase; Okadaic acid; Oxidative stress; Pathology; Phosphoprotein phosphatase; Phosphorylation; Phytotherapy; Plant Extracts - pharmacology; Protein phosphatase; Proteins; tau; Tau protein; tau Proteins - antagonists & inhibitors; Transfection; Tumor necrosis factor-TNF; Zingiberaceae - chemistry; tau; Alzheimer’s disease; glycogen synthase kinase 3β; eupatin; neuroinflammation
• DOI: 10.3390/molecules25235652
• EISSN: 1420-3049

Alzheimer's disease (AD), which is among the most prevalent neurodegenerative diseases, manifests as increasing memory loss and cognitive decline. Tau phosphorylation and aggregation are strongly linked to neurodegeneration, as well as associated with chronic neuroinflammatory processes. The anti-inflammation effects of natural products have led to wide recognition of their potential for use in treating and preventing AD. This study investigated whether eupatin, a polymethoxyflavonoid found in
species, has inhibitory effects on neuroinflammation and tau phosphorylation. We treated mouse macrophages and microglia cells with lipopolysaccharides (LPSs) to activate inflammatory signals, and we treated neuronal cells with a protein phosphatase 2A inhibitor, okadaic acid (OA), or transfection with pRK5-EGFP-Tau P301L plasmid to induce tau phosphorylation. The results indicated that eupatin significantly reduced the LPS-induced protein expression and phosphorylation of p65 and inducible nitric oxide synthase as well as downstream products interleukin 6 and nitrite, respectively. Furthermore, eupatin markedly inhibited the expression of phospho-tau in response to OA treatment and plasmid transfection. We discovered that this inhibition was achieved through the inhibition of glycogen synthase kinase 3β (GSK3β), and molecular docking results suggested that eupatin can sufficiently bind to the GSK3β active site. Our results demonstrate that eupatin has neuroprotective effects, making it suitable for AD treatment.